Angiogenesis in Synchronous and Metachronous Colorectal Liver Metastases The Liver as a Permissive Soil

Gesiena E. van der Wal, Annette S. H. Gouw, Jan A. A. M. Kamps, Henk E. Moorlag, Marian L. C. Bulthuis, Grietje Molema, Koert P. de Jong*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

49 Citations (Scopus)

Abstract

Objective: Resection of a primary colorectal carcinoma (CRC) can be accompanied by rapid outgrowth of liver metastases, suggesting a role for angiogenesis. The aim of this study is to investigate whether the presence of a primary CRC is associated with changes in angiogenic status and proliferation/apoptotic rate in synchronous liver metastases and/or adjacent liver parenchyma.

Methods: Gene expression and localization of CD31, HIF-1 alpha, members of the vascular endothelial growth factor (VEGF) and Angiopoietin (Ang) system were studied using qRT-PCR and immunohistochemistry in colorectal liver metastases and nontumorous-adjacent liver parenchyma. Proliferation and apoptotic rate were quantified. Three groups of patients were included: (1) simultaneous resection of synchronous liver metastases and primary tumor (SS-group), (2) resection of synchronous liver metastases 3 to 12 months after resection of the primary tumor [late synchronous (LS-group)], and (3) resection of metachronous metastases >14 months after resection of the primary tumor (M-group).

Results: In all 3 groups a higher expression of the angiogenic factors was encountered in adjacent liver parenchyma as compared to the metastases. VEGFR-2 gene expression was abundant in adjacent liver parenchyma in all 3 groups. VEGF-A and VEGFR-1 were prominent in adjacent parenchyma in the SS-group. The SS-group showed the highest Ang-2/Ang-1 ratio both in the metastases and the adjacent liver. This was accompanied by a high turnover of tumor cells.

Conclusion: In the presence of the primary tumor, the liver parenchyma adjacent to the synchronous liver metastases provides an angiogenic prosperous environment for metastatic tumor growth.

Original languageEnglish
Pages (from-to)86-94
Number of pages9
JournalAnnals of Surgery
Volume255
Issue number1
DOIs
Publication statusPublished - Jan-2012

Keywords

  • HUMAN HEPATOCELLULAR-CARCINOMA
  • ENDOTHELIAL GROWTH-FACTOR
  • E-SELECTIN
  • TUMOR DORMANCY
  • TRANSENDOTHELIAL MIGRATION
  • PREMETASTATIC NICHE
  • CANCER-PATIENTS
  • BILIARY TREE
  • CELLS
  • EXPRESSION

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